Disease relevance of Phgdh

• The full-length rat 3-phosphoglycerate dehydrogenase was expressed in E. coli and purified [1].
• The deduced amino acid sequence (533 residues; Mr 56493) shared closer similarity with Bacillus subtilis 3-phosphoglycerate dehydrogenase than with the enzymes from Escherichia coli, Haemophilus influenzae and Saccharomyces cerevisiae [1].
• D-3-Phosphoglycerate dehydrogenase from Mycobacterium tuberculosis is a link between the Escherichia coli and mammalian enzymes [2].
• The activity of 3-phosphoglycerate dehydrogenase was high in tissues of high cell-renewal capacity, and was increased in neonatal and regenerating liver and, more markedly, in hepatomas [3].
• The activities of 3-phosphoglycerate dehydrogenase, an enzyme of serine biosynthesis, and serine hydroxymethyltransferase, serine dehydratase and serine aminotransferase, which are competing enzymes of serine utilization, were assayed in human colon carcinomas from patients and in transplantable rat sarcomas [4].

High impact information on Phgdh

• By contrast, the Bergman glia, a native astroglia in the cerebellar cortex, highly expresses 3PGDH [5].
• The enzymes of the "phosphorylated pathway" of serine biosynthesis, i.e., 3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase and phosphoserine phosphatase are present in rat brain as well as in rat astroglia-rich primary cultures and their specific activities have been determined [6].
• Cysteine, but not methionine, inhibited the accumulation of 3-PGDH mRNA in FTO2B hepatoma cells [7].
• In conclusion, the dietary control of the expression of the 3-PGDH gene in liver seems to involve the negative effects of cysteine and glucagon and the positive effect of insulin [7].
• Shifting rats to a protein-free, carbohydrate-rich diet, although not starvation, resulted in the appearance of mRNA for, and activity of, 3-phosphoglycerate dehydrogenase (3-PGDH) in liver as well as in a marked decrease in plasma cystine concentration [7].

Biological context of Phgdh

• Selective expression of L-serine synthetic enzyme 3PGDH in schwann cells, perineuronal glia, and endoneurial fibroblasts along rat sciatic nerves and its upregulation after crush injury [8].

Anatomical context of Phgdh

• In hepatocytes in primary culture, cysteine plus methionine and glucagon had, independently, an approx. 4-fold inhibitory effect on the abundance of the 3-PGDH mRNA and caused its almost complete disappearance when tested together [7].
• In frozen sections from rat forebrain, only astrocytes were immunoreactive for 3PGDH [9].
• In contrast, 3PGDH was immunonegative in axons, somata of spinal motoneurons and ganglion cells, and endoneurial macrophages [8].
• Here we pursued 3PGDH expression in peripheral nerves and its change after crush injury [8].
• In the pathway of rat sciatic nerves, 3PGDH was selectively expressed in non-neuronal elements: Schwann sheaths and endoneurial fibroblasts in sciatic nerves, satellite cells in dorsal root ganglia, and astrocytes and oligodendrocytes in the spinal ventral horn [8].

Associations of Phgdh with chemical compounds

• By contrast with the bacterial enzyme, rat 3-phosphoglycerate dehydrogenase did not catalyse the reduction of 2-oxoglutarate, indicating that this enzyme is not involved in human D- or L-hydroxyglutaric aciduria [1].
• This increase in specific activity was maximal 72 h after injection of testosterone in the case of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase [10].
• Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver [7].
• The expression of an enzyme 3-phosphoglycerate dehydrogenase (3PGDH), which is essential for L-Ser biosynthesis from a glycolytic intermediate 3-phosphoglycerate, was investigated [9].
• The disequilibrium in the pathway in rat liver is nearly equally divided between the L-phosphoserine phosphatase (EC 3.1.3.3) step and the other two reactions [D-3-phosphoglycerate dehydrogenase (EC 1.1.1.95) and L-phosphoserine aminotransferase (EC 2.6.1.52)], whereas in rabbit the phosphatase reaction accounts for nearly the entire delta G [11].

Analytical, diagnostic and therapeutic context of Phgdh

• Castration had no effect on the specific activity of these enzymes in the kidney; however, 3-phosphoglycerate dehydrogenase was significantly diminished in the liver 6 days after castration [10].
• As revealed by Western blotting and immunocytochemical staining, 3PGDH-protein expression in vitro was the highest in astrocytes, intermediate in neurons and the lowest in microglial cells [9].
• Feeding the rat a low protein diet, however, induced the activity of D-3-phosphoglycerate dehydrogenase 12-fold, that of L-phosphoserine aminotransferase 20-fold, and that of L-phosphoserine phosphatase 2-fold [11].

References